Details for: HIRIP3

Gene ID: 8479

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HIRIP3

Ensembl ID: ENSG00000149929

Description: HIRA interacting protein 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural progenitor cell CL0011020
    CSI 6.6
    rCSI 29.04%
    PRS 83.12
  • neural crest cell CL0011012
    CSI 3.94
    rCSI 3.11%
    PRS 86.88
  • naive T cell CL0000898
    CSI 3.57
    rCSI 2.48%
    PRS 98.41
  • ciliated epithelial cell CL0000067
    CSI 3.29
    rCSI 2.89%
    PRS 85.01
  • ON-bipolar cell CL0000749
    CSI 3.27
    rCSI 4.86%
    PRS 91.28
  • respiratory basal cell CL0002633
    CSI 3.05
    rCSI 3.16%
    PRS 93.87
  • early lymphoid progenitor CL0000936
    CSI 2.98
    rCSI 2.62%
    PRS 95.17
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.86
    rCSI 2.47%
    PRS 94.25
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.8
    rCSI 3.24%
    PRS 85.87
  • myofibroblast cell CL0000186
    CSI 2.78
    rCSI 3.85%
    PRS 89.8
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.73
    rCSI 1.91%
    PRS 95.22
  • rod bipolar cell CL0000751
    CSI 2.64
    rCSI 4.75%
    PRS 88.34
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.58
    rCSI 7.62%
    PRS 92.23
  • common myeloid progenitor CL0000049
    CSI 2.54
    rCSI 2.05%
    PRS 93.61
  • bronchus fibroblast of lung CL2000093
    CSI 2.36
    rCSI 1.92%
    PRS 91.93
  • radial glial cell CL0000681
    CSI 2.29
    rCSI 3.19%
    PRS 91.04
  • retinal cone cell CL0000573
    CSI 2.23
    rCSI 3.58%
    PRS 85.79
  • myeloid leukocyte CL0000766
    CSI 2.22
    rCSI 2.05%
    PRS 93.7
  • multi-ciliated epithelial cell CL0005012
    CSI 2.2
    rCSI 2.2%
    PRS 87.64
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.14
    rCSI 2.75%
    PRS 89.35
  • OFF-bipolar cell CL0000750
    CSI 2.13
    rCSI 2.91%
    PRS 90.82
  • lung ciliated cell CL1000271
    CSI 2.12
    rCSI 2.45%
    PRS 88
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.12
    rCSI 1.91%
    PRS 91.63
  • retina horizontal cell CL0000745
    CSI 2.03
    rCSI 3.09%
    PRS 89.78
  • promyelocyte CL0000836
    CSI 1.98
    rCSI 2.85%
    PRS 94.16
  • basal cell CL0000646
    CSI 1.95
    rCSI 2.61%
    PRS 90.13
  • keratinocyte CL0000312
    CSI 1.93
    rCSI 1.61%
    PRS 92.33
  • vascular associated smooth muscle cell CL0000359
    CSI 1.88
    rCSI 6.11%
    PRS 90.98
  • mesenchymal cell CL0008019
    CSI 1.82
    rCSI 4.63%
    PRS 88.4
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.82
    rCSI 3.21%
    PRS 81.16
  • retinal bipolar neuron CL0000748
    CSI 1.82
    rCSI 3.4%
    PRS 85.53
  • promonocyte CL0000559
    CSI 1.78
    rCSI 3.04%
    PRS 93.94
  • common dendritic progenitor CL0001029
    CSI 1.71
    rCSI 2.14%
    PRS 96.16
  • peripheral nervous system neuron CL2000032
    CSI 1.67
    rCSI 2.28%
    PRS 86.98
  • mammary gland epithelial cell CL0002327
    CSI 1.61
    rCSI 5.65%
    PRS 95.64
  • glioblast CL0000030
    CSI 1.58
    rCSI 2.53%
    PRS 86.1
  • large pre-B-II cell CL0000957
    CSI 1.16
    rCSI 3.3%
    PRS 92.16
  • forebrain radial glial cell CL0013000
    CSI 1.03
    rCSI 3.3%
    PRS 92.4
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.77
    rCSI 2.22%
    PRS 91.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HIRIP3](/details-gene/8479) (HIRA Interacting Protein 3) is a protein-coding gene located on chromosome 16p11.2. Functionally, it is a nuclear protein known to participate in chromatin organization and histone chaperone activity, primarily through its interaction with the HIRA histone chaperone complex ([Link](https://doi.org/10.1128/mcb.18.9.5546)). Expression data indicates that **Overall**, [HIRIP3](/details-gene/8479) shows the highest significance in progenitor cell populations, particularly in [neural progenitor cell](/details-cell/CL0011020)s and [neural crest cell](/details-cell/CL0011012)s, as well as various hematopoietic progenitors. This expression pattern, combined with its molecular function, suggests a fundamental role in processes requiring dynamic chromatin remodeling, such as cell differentiation and proliferation. ## Cellular Roles and Expression Landscape The expression profile of [HIRIP3](/details-gene/8479) highlights its significant role across multiple developmental and progenitor lineages. **Overall**, the gene's highest significance is observed in cells of the developing nervous system, including [neural progenitor cell](/details-cell/CL0011020) (CSI: 6.60), [neural crest cell](/details-cell/CL0011012) (CSI: 3.94), and various bipolar and interneuron cell types. This is consistent with a crucial function in neurogenesis. Beyond the nervous system, [HIRIP3](/details-gene/8479) is also a significant gene in hematopoietic progenitors, such as [early lymphoid progenitor](/details-cell/CL0000936)s, [granulocyte monocyte progenitor cell](/details-cell/CL0000557)s, and [common myeloid progenitor](/details-cell/CL0000049)s. Its notable expression in these diverse, highly proliferative progenitor populations suggests that [HIRIP3](/details-gene/8479) is not restricted to a single lineage but rather plays a more general role in establishing or maintaining the chromatin landscape necessary for cell division and subsequent differentiation. The gene also shows relevance in some differentiated cell types that may require active chromatin maintenance, such as [naive T cell](/details-cell/CL0000898)s and [ciliated epithelial cell](/details-cell/CL0000067)s. ## Pathways and Molecular Function [HIRIP3](/details-gene/8479) is primarily localized to the [nucleus](/details-cell/GO:0005634), including the [nucleoplasm](/details-cell/GO:0005654) and [nucleolus](/details-cell/GO:0005730). Its key annotated functions relate to the structural maintenance of the genome. It is involved in the biological process of [chromatin organization](/details-cell/GO:0006325) and has a specific molecular function as a [H2a-h2b histone complex chaperone](/details-cell/GO:0000511). Research has established that [HIRIP3](/details-gene/8479) is a nuclear phosphoprotein that directly binds to the HIRA complex and core histones, suggesting a direct role in the deposition of histones onto DNA ([Link](https://doi.org/10.1128/mcb.18.9.5546)). The protein is also a substrate for the serine-threonine kinase CK2, indicating that its activity may be regulated by post-translational modification ([Link](https://doi.org/10.1515/bc.2007.045)). This role as a histone chaperone is consistent with its high expression in rapidly dividing progenitor cells, which require constant synthesis and assembly of new chromatin. ## Research Directions The functional data for [HIRIP3](/details-gene/8479) as a chromatin organizer, combined with its specific expression pattern in progenitor cells, gives rise to several testable hypotheses. 1. Given its high significance in diverse progenitor populations (neural, hematopoietic), [HIRIP3](/details-gene/8479) may function as a master regulator of stemness by maintaining an open and plastic chromatin state. Its downregulation could be a prerequisite for terminal differentiation across multiple lineages. 2. The phosphorylation of [HIRIP3](/details-gene/8479) by CK2 ([Link](https://doi.org/10.1515/bc.2007.045)) may serve as a regulatory switch that dictates its binding affinity for either the HIRA complex or histones, thereby controlling the timing of replication-independent histone deposition during specific phases of the cell cycle or differentiation. To test the first hypothesis, a key experiment would be to use a CRISPR-Cas9-based knockout or knockdown system for [HIRIP3](/details-gene/8479) in human pluripotent stem cells. These modified cells could then be directed to differentiate down neural and hematopoietic lineages. The effects of [HIRIP3](/details-gene/8479) loss could be assayed by single-cell RNA sequencing (scRNA-seq) to determine if differentiation trajectories are altered, accelerated, or stalled, and by ATAC-seq to assess corresponding changes in chromatin accessibility at lineage-specific gene loci. From a therapeutic perspective, [HIRIP3](/details-gene/8479) presents a potential target in diseases of uncontrolled proliferation, such as cancer, particularly those characterized by a stem-like or de-differentiated phenotype. As a crucial component of chromatin assembly, its inhibition could selectively halt the growth of rapidly dividing cancer cells. Therefore, developing small molecule inhibitors that disrupt the interaction between [HIRIP3](/details-gene/8479) and the HIRA complex could be a viable therapeutic strategy. However, its broad importance in healthy progenitor cells suggests that systemic inhibition would likely lead to significant toxicity, necessitating targeted drug delivery approaches.

Genular Protein ID: 671088468

Symbol: HIRP3_HUMAN

Name: HIRA-interacting protein 3

UniProtKB Accession Codes:

Q9BW71 H3BSR3 O75707 O75708

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 6 Ensembl 2 GO 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9710638

Title: Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA.

PubMed ID: 9710638

DOI: 10.1128/mcb.18.9.5546

PubMed ID: 17391060

Title: HIRIP3 is a nuclear phosphoprotein interacting with and phosphorylated by the serine-threonine kinase CK2.

PubMed ID: 17391060

DOI: 10.1515/bc.2007.045

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 16964243

Title: A probability-based approach for high-throughput protein phosphorylation analysis and site localization.

PubMed ID: 16964243

DOI: 10.1038/nbt1240

PubMed ID: 19367720

Title: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment.

PubMed ID: 19367720

DOI: 10.1021/pr800500r

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 38334665

Title: Identification and Characterization of HIRIP3 as a Histone H2A Chaperone.

PubMed ID: 38334665

DOI: 10.3390/cells13030273

Sequence Information:

  • Length: 556
  • Mass: 61957
  • Checksum: ACABE2E0032B8C13
  • Sequence:
    • MAREKEMQEF TRSFFRGRPD LSTLTHSIVR RRYLAHSGRS HLEPEEKQAL KRLVEEELLK 
MQVDEAASRE DKLDLTKKGK RPPTPCSDPE RKRFRFNSES ESGSEASSPD YFGPPAKNGV 
AAEVSPAKEE NPRRASKAVE ESSDEERQRD LPAQRGEESS EEEEKGYKGK TRKKPVVKKQ 
APGKASVSRK QAREESEESE AEPVQRTAKK VEGNKGTKSL KESEQESEEE ILAQKKEQRE 
EEVEEEEKEE DEEKGDWKPR TRSNGRRKSA REERSCKQKS QAKRLLGDSD SEEEQKEAAS 
SGDDSGRDRE PPVQRKSEDR TQLKGGKRLS GSSEDEEDSG KGEPTAKGSR KMARLGSTSG 
EESDLEREVS DSEAGGGPQG ERKNRSSKKS SRKGRTRSSS SSSDGSPEAK GGKAGSGRRG 
EDHPAVMRLK RYIRACGAHR NYKKLLGSCC SHKERLSILR AELEALGMKG TPSLGKCRAL 
KEQREEAAEV ASLDVANIIS GSGRPRRRTA WNPLGEAAPP GELYRRTLDS DEERPRPAPP 
DWSHMRGIIS SDGESN